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1.
Angew Chem Int Ed Engl ; : e202411217, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39103975

RESUMEN

Hole-transporting materials (HTMs) are crucial for obtaining the stability and high efficiency of perovskite solar cells (PSCs). However, the current state-of-the-art n-i-p PSCs relied on the use of 2,2',7,7'-tetrakis(N,N-di-p-methoxyphenylamine)-9,9'-spirobifluorene (spiro-OMeTAD) exhibit inferior intrinsic and ambient stability due to the p-dopant and hydrophilic Li-TFSI additive. In this study, a new spiro-type HTM with a critical quasi-planar core (Z-W-03) is developed to improve both the thermal and ambient stability of PSCs. The results suggest that the planar carbazole structure effectively passivates the trap states compared to the triphenylamine with a propeller-like conformation in spiro-OMeTAD. This passivation effect leads to the shallower trap states when the quasi-planar HTMs interact with the Pb-dimer. Consequently, the device using Z-W-03 achieves a higher Voc of 1.178 V compared to the spiro-OMeTAD's 1.155 V, resulting in an enhanced efficiency of 24.02%. In addition, the double-column π-π stacking of Z-W-03 results in high hole mobility (~10-4 cm2 V-1 s-1) even without p-dopant. Moreover, when the surface interface is modified, the undoped Z-W-03 device can achieve an efficiency of nearly 23%. Compared to the PSCs using spiro-OMeTAD, those with Z-W-03 exhibit enhanced stability under N2 and ambient conditions.

2.
Math Biosci Eng ; 21(4): 5308-5334, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38872537

RESUMEN

Tuberculosis has affected human beings for thousands of years, and until today, tuberculosis still ranks third among 29 infectious diseases in China. However, most of the existing mathematical models consider a single factor, which is not conducive to the study of tuberculosis transmission dynamics. Therefore, this study considers the combined effects of vaccination, treatment, and contaminated environments on tuberculosis, and builds a new model with seven compartments of $ SVEITRW $ based on China's tuberculosis data. The study shows that when the basic reproduction number $ R_{0} $ is less than 1, the disease will eventually disappear, but when $ R_{0} $ is greater than 1, the disease may persist. In the numerical analysis part, we use Markov-chain Monte-Carlo method to obtain the optimal parameters of the model. Through the next generation matrix theory, we calculate that the $ R_{0} $ value of tuberculosis in China is $ 2.1102 $, that is, if not controlled, tuberculosis in China will not disappear over time. At the same time, through partial rank correlation coefficients, we find the most sensitive parameter to the basic reproduction number $ R_{0} $. On this basis, we combine the actual prevalence of tuberculosis in China, apply Pontryagin's maximum principle, and perform cost-effectiveness analysis to obtain the conditions required for optimal control. The analysis shows that four control strategies could effectively reduce the prevalence of TB, and simultaneously controlling $ u_{2}, u_{3}, u_{4} $ is the most cost-effective control strategy.


Asunto(s)
Número Básico de Reproducción , Cadenas de Markov , Método de Montecarlo , Tuberculosis , Vacunación , Humanos , China/epidemiología , Tuberculosis/prevención & control , Tuberculosis/epidemiología , Vacunación/economía , Simulación por Computador , Prevalencia , Modelos Teóricos , Algoritmos , Antituberculosos/uso terapéutico
3.
BMJ Open ; 14(6): e083100, 2024 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-38910008

RESUMEN

OBJECTIVES: To investigate the knowledge, attitude and practice (KAP) towards insomnia and sleep hygiene among patients with chronic insomnia. DESIGN: Web-based cross-sectional survey. SETTING: Shaanxi Provincial People's Hospital (northwest China) between January 2023 and May 2023. PARTICIPANTS: Patients with chronic insomnia. PRIMARY AND SECONDARY OUTCOME MEASURES: Demographic characteristics and KAP towards insomnia and sleep hygiene were collected by distributing a questionnaire developed by the authors. RESULTS: A total of 613 people participated in this study, with a Mean Knowledge Score of 7.63±2.56 (total score of 12), a Mean Attitude Score of 48.39±6.643 (total score of 70) and a Mean Practice Score of 42.37±8.592 (total score of 70). Knowledge was significantly correlated with attitude (r=0.447, p<0.001) and practice (r=0.327, p<0.001), and attitude was significantly correlated with practice (r=0.486, p<0.001). Multivariable logistic regression showed that higher knowledge (OR=1.181 (1.062-1.314), p=0.002) and better attitude (OR=1.171 (1.124-1.221), p<0.001) were independently associated with good practice. According to the structural equation modelling analysis, knowledge directly influenced practice (ß=0.457, p=<0.001) and attitude (ß=1.160, p=<0.001), while attitude influenced practice (ß=0.550, p=<0.001). CONCLUSION: The KAP towards insomnia and sleep hygiene among patients with chronic insomnia in Northwest China in 2023 was moderate, with better practice showing signs of being influenced by better knowledge and more positive attitudes.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Higiene del Sueño , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Estudios Transversales , Femenino , Masculino , China/epidemiología , Persona de Mediana Edad , Adulto , Encuestas y Cuestionarios , Enfermedad Crónica , Modelos Logísticos , Anciano , Adulto Joven
4.
J Cell Mol Med ; 28(11): e18366, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38856956

RESUMEN

Ischemic stroke is one of the main causes of disability and death. However, recanalization of occluded cerebral arteries is effective only within a very narrow time window. Therefore, it is particularly important to find neuroprotective biological targets for cerebral artery recanalization. Here, gene expression profiles of datasets GSE160500 and GSE97537 were downloaded from the GEO database, which were related to ischemic stroke in rats. Olfactory receptor 78 (Olfr78) was screened, and which highly associated with Calcium signalling pathway and MAPK pathway. Interacting protein of Olfr78, Prkaca, was predicted by STRING, and their interaction was validated by Co-IP analysis. Then, a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) and a neuronal cell model stimulated by oxygen-glucose deprivation/reoxygenation (OGD/R) were constructed, and the results showed that expression of Olfr78 and Prkaca was downregulated in MCAO rats and OGD/R-stimulated neurons. Overexpression of Olfr78 or Prkaca inhibited the secretion of inflammatory factors, Ca2+ overload, and OGD/R-induced neuronal apoptosis. Moreover, Overexpression of Prkaca increased protein levels of cAMP, PKA and phosphorylated p38 in OGD/R-stimulated neurons, while SB203580, a p38 inhibitor, treatment inhibited activation of the cAMP/PKA-MAPK pathway and counteracted the effect of Olfr78 overexpression on improvement of neuronal functions. Meanwhile, overexpression of Olfr78 or Prkaca markedly inhibited neuronal apoptosis and improved brain injury in MCAO/R rats. In conclusion, overexpression of Olfr78 inhibited Ca2+ overload and reduced neuronal apoptosis in MCAO/R rats by promoting Prkaca-mediated activation of the cAMP/PKA-MAPK pathway, thereby improving brain injury in cerebral ischaemia-reperfusion.


Asunto(s)
Apoptosis , AMP Cíclico , Ratas Sprague-Dawley , Receptores Odorantes , Daño por Reperfusión , Animales , Daño por Reperfusión/metabolismo , Daño por Reperfusión/genética , Ratas , Masculino , AMP Cíclico/metabolismo , Receptores Odorantes/metabolismo , Receptores Odorantes/genética , Isquemia Encefálica/metabolismo , Isquemia Encefálica/genética , Isquemia Encefálica/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/etiología , Lesiones Encefálicas/patología , Neuronas/metabolismo , Modelos Animales de Enfermedad , Infarto de la Arteria Cerebral Media/metabolismo , Transducción de Señal
5.
World J Diabetes ; 15(5): 945-957, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38766429

RESUMEN

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a debilitating complication of diabetes mellitus with limited available treatment options. Radix Salviae, a traditional Chinese herb, has shown promise in treating DPN, but its therapeutic mech-anisms have not been systematically investigated. AIM: Radix Salviae (Danshen in pinin), a traditional Chinese medicine (TCM), is widely used to treat DPN in China. However, the mechanism through which Radix Salviae treats DPN remains unclear. Therefore, we aimed to explore the mechanism of action of Radix Salviae against DPN using network pharmacology. METHODS: The active ingredients and target genes of Radix Salviae were screened using the TCM pharmacology database and analysis platform. The genes associated with DPN were obtained from the Gene Cards and OMIM databases, a drug-com-position-target-disease network was constructed, and a protein-protein inter-action network was subsequently constructed to screen the main targets. Gene Ontology (GO) functional annotation and pathway enrichment analysis were performed via the Kyoto Encyclopedia of Genes and Genomes (KEGG) using Bioconductor. RESULTS: A total of 56 effective components, 108 targets and 4581 DPN-related target genes of Radix Salviae were screened. Intervention with Radix Salviae for DPN mainly involved 81 target genes. The top 30 major targets were selected for enrichment analysis of GO and KEGG pathways. CONCLUSION: These results suggested that Radix Salviae could treat DPN by regulating the AGE-RAGE signaling pathway and the PI3K-Akt signaling pathway. Therefore, Danshen may affect DPN by regulating inflammation and apoptosis.

6.
PLoS One ; 19(5): e0299522, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38696452

RESUMEN

Hepatocellular carcinoma (HCC) is the most common primary liver cancer worldwide and no pharmacological treatment is available that can achieve complete remission of HCC. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a recently identified HCC tumor suppressor gene which plays an important role in the development of HCC and its inactivation and reactivation has been shown to result in respectively HCC tumorigenesis and suppression. Small activating RNAs (saRNAs) have been used to achieve targeted activation of therapeutic genes for the restoration of their encoded protein through the RNAa mechanism. Here we designed and validated saRNAs that could activate LHPP expression at both the mRNA and protein levels in HCC cells. Activation of LHPP by its saRNAs led to the suppression of HCC proliferation, migration and the inhibition of Akt phosphorylation. When combined with targeted anticancer drugs (e.g., regorafenib), LHPP saRNA exhibited synergistic effect in inhibiting in vitro HCC proliferation and in vivo antitumor growth in a xenograft HCC model. Findings from this study provides further evidence for a tumor suppressor role of LHPP and potential therapeutic value of restoring the expression of LHPP by saRNA for the treatment of HCC.


Asunto(s)
Carcinoma Hepatocelular , Proliferación Celular , Pirofosfatasa Inorgánica , Neoplasias Hepáticas , Humanos , Pirofosfatasa Inorgánica/metabolismo , Pirofosfatasa Inorgánica/genética , Proliferación Celular/efectos de los fármacos , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Ratones , Línea Celular Tumoral , Regulación hacia Arriba/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Movimiento Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ratones Desnudos
7.
Cell Death Differ ; 31(6): 738-752, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38594444

RESUMEN

Glioblastoma (GBM) is the most aggressive malignant primary brain tumor characterized by a highly heterogeneous and immunosuppressive tumor microenvironment (TME). The symbiotic interactions between glioblastoma stem cells (GSCs) and tumor-associated macrophages (TAM) in the TME are critical for tumor progression. Here, we identified that IFI35, a transcriptional regulatory factor, plays both cell-intrinsic and cell-extrinsic roles in maintaining GSCs and the immunosuppressive TME. IFI35 induced non-canonical NF-kB signaling through proteasomal processing of p105 to the DNA-binding transcription factor p50, which heterodimerizes with RELB (RELB/p50), and activated cell chemotaxis in a cell-autonomous manner. Further, IFI35 induced recruitment and maintenance of M2-like TAMs in TME in a paracrine manner. Targeting IFI35 effectively suppressed in vivo tumor growth and prolonged survival of orthotopic xenograft-bearing mice. Collectively, these findings reveal the tumor-promoting functions of IFI35 and suggest that targeting IFI35 or its downstream effectors may provide effective approaches to improve GBM treatment.


Asunto(s)
Glioblastoma , FN-kappa B , Células Madre Neoplásicas , Transducción de Señal , Macrófagos Asociados a Tumores , Glioblastoma/metabolismo , Glioblastoma/patología , Glioblastoma/genética , Humanos , Animales , Ratones , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/patología , FN-kappa B/metabolismo , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Línea Celular Tumoral , Microambiente Tumoral
8.
Exp Ther Med ; 27(4): 135, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38476886

RESUMEN

Dysregulation of autophagy has previously been associated with the formation of toxic proteins, such as α-synuclein, in patients with Parkinson's disease (PD). In addition, it has been indicated that programmed cell death 4 (PDCD4) can inhibit autophagy in certain conditions, such as diabetic nephropathy, atherosclerosis and cardiac hypertrophy. Therefore, the hypothesis that PDCD4 can promote dopaminergic neuron damage through autophagy was proposed. To explore this hypothesis, the present study treated human neuroblastoma SK-N-SH cells with 1-methyl-4-phenylpyridinium (MPP+) to establish an in vitro model of PD. The potential effects of PDCD4 knockdown on lactate dehydrogenase (LDH) release, cell apoptosis, inflammatory response, oxidative stress and autophagy were then evaluated in this model of PD using an LDH assay kit, flow cytometry, western blotting, ELISA and immunofluorescence. The autophagy inhibitor 3-methyladenine (3-MA) was also applied to treat these cells, and its effects on these aforementioned parameters following PDCD4 knockdown were assessed. MPP+ was shown to increase the expression levels of PDCD4 in SK-N-SH cells. PDCD4 knockdown was revealed to suppress LDH release, cell apoptosis, secretion of inflammatory factors and oxidative stress. In addition, PDCD4 knockdown was demonstrated to enhance autophagy in cells treated with MPP+. By contrast, 3-MA treatment reversed the aforementioned effects of PDCD4 knockdown on cells, suggesting autophagy to be among the processes regulated by PDCD4 in SK-N-SH cells. The results of the present study suggested the existence of regulatory effects mediated by PDCD4 on autophagy in MPP+-induced SK-N-SH cells, offering potential future targets for PD therapy.

9.
J Sci Food Agric ; 104(10): 6174-6185, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38459926

RESUMEN

BACKGROUND: Pseudostellaria heterophylla is a Chinese medicine and healthy edible that is widely used to for its immunomodulatory, antioxidant, antidiabetic and antitussive properties. However, the potential function of P. heterophylla in intestinal microecology remains unclear. In this study, we investigated the impact of P. heterophylla on immune functions and evaluated its potential to regulate the gut microbiota and metabolome. RESULTS: The results showed that P. heterophylla significantly increased the content of red blood cells, total antioxidant capacity and expression of immune factors, and decreased platelet counts when compared to the control under cyclophosphamide injury. In addition, P. heterophylla altered the diversity and composition of the gut bacterial community; increased the abundance of potentially beneficial Akkermansia, Roseburia, unclassified Clostridiaceae, Mucispirillum, Anaeroplasma and Parabacteroides; and decreased the relative abundance of pathogenic Cupriavidus and Staphylococcus in healthy mice. Metabolomic analyses showed that P. heterophylla significantly increased the content of functional oligosaccharides, common oligosaccharides, vitamins and functional substances. Probiotics and pathogens were regulated by metabolites across 11 pathways in the bacterial-host co-metabolism network. CONCLUSION: We demonstrated that P. heterophylla increased the abundance of probiotics and decreased pathogens, and further stimulated host microbes to produce beneficial secondary metabolites for host health. Our studies highlight the role of P. heterophylla in gut health and provide new insights for the development of traditional Chinese medicine in the diet. © 2024 Society of Chemical Industry.


Asunto(s)
Bacterias , Microbioma Gastrointestinal , Animales , Ratones , Bacterias/clasificación , Bacterias/metabolismo , Bacterias/genética , Bacterias/aislamiento & purificación , Intestinos/microbiología , Masculino , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/metabolismo , Metaboloma , Humanos
10.
J Matern Fetal Neonatal Med ; 37(1): 2313356, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38342577

RESUMEN

INTRODUCTION: It is still no consensus on the use of ropivacaine or bupivacaine in epidural anesthesia for cesarean section (CS), because their anesthetic potency and relative complications remains controversial. This system review and meta-analysis aimed to compare the efficacy of epidural ropivacaine and bupivacaine for elective CSs and investigate relative complications for parturients and neonates. METHODS: We searched PubMed, MEDLINE, Embase, Cochrane Library, Science-Direct, and Google Scholar to June 30, 2023 for randomized controlled trials (RCTs), which compared epidural ropivacaine with bupivacaine for elective CSs. The success rate of epidural anesthesia (EA) was primary outcome. The secondary outcomes included onset times of sensory block, maternal side effects, neonatal Apgar scores and umbilical artery pH. RESULTS: We analyzed 8 RCTs with 532 parturients. 0.75% ropivacaine is associated with a shorter onset time of sensory block than 0.5% bupivacaine (SMD = -0.43, 95% CI: -0.70 to -0.17; p = .001). 0.5% ropivacaine resulted in a reduced nausea than 0.5% bupivacaine (RR = 0.49, 95% CI: 0.28 to 0.83; p = .008). In addition, there were no significant difference between ropivacaine and bupivacaine groups in terms of success rate of epidural anesthesia, maternal side effects (hypotension, bradycardia, shivering), and neonatal Apgar scores and umbilical artery pH. CONCLUSIONS: The findings suggest that there were no significant difference between epidural ropivacaine and bupivacaine for elective CSs in terms of the success rate (85.9% vs. 83.5), maternal side effects (hypotension, bradycardia, shivering), and neonatal Apgar scores and umbilical artery pH. But compared with 0.5% bupivacaine, epidural 0.75% ropivacaine was mildly effective for reducing onset time of sensory block and 0.5% ropivacaine reduced the incidence of maternal nausea.


Asunto(s)
Anestesia Epidural , Anestesia Obstétrica , Bupivacaína , Cesárea , Ropivacaína , Femenino , Humanos , Recién Nacido , Embarazo , Anestesia Epidural/métodos , Anestesia Epidural/efectos adversos , Anestesia Obstétrica/efectos adversos , Anestesia Obstétrica/métodos , Anestésicos Locales/administración & dosificación , Puntaje de Apgar , Bupivacaína/administración & dosificación , Bupivacaína/efectos adversos , Cesárea/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Ropivacaína/administración & dosificación
11.
Eur J Med Res ; 29(1): 101, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38321571

RESUMEN

Iron metabolism disorders are implicated in the pathogenesis of Alzheimer's disease (AD). It was previously reported that transferrin receptor (TFR1) expression was upregulated in AD mouse model. However, the precise biological functions of TFR1 in AD progression remains unclear. Herein, we observed a gradual increase in TFR1 protein expression during the differentiation of AD patient-derived induced pluripotent stem cells (AD-iPS). TFR1 knockdown inhibited the protein expression of ferritin and ferritin heavy chain 1 (FTH1), enhanced the expression of ferroportin 1 (FPN1), and decreased intracellular levels of total iron, labile iron, and reactive oxygen species (ROS). Moreover, TFR1 knockdown improved mitochondrial membrane potential (MMP), increased adenosine triphosphate (ATP) content, downregulated mitochondrial fission proteins, and upregulated mitochondrial fusion proteins. TFR1 knockdown alleviated iron overload and mitochondrial dysfunction in neural cells differentiated from AD-iPS, while TFR1 overexpression showed the opposite results. Additionally, TFR1interacted with glycogen synthase kinase 3 beta (GSK3B) and promoted GSK3B expression. GSK3B overexpression reversed the inhibitory effects of TFR1 knockdown on iron overload and mitochondrial dysfunction in AD-iPS differentiated neural cells. In conclusion, TFR1 knockdown alleviated iron overload and mitochondrial dysfunction in neural cells differentiated from AD-iPS by promoting GSK3B expression. Our findings provide a potential therapeutic target for the treatment of AD.


Asunto(s)
Enfermedad de Alzheimer , Células Madre Pluripotentes Inducidas , Sobrecarga de Hierro , Enfermedades Mitocondriales , Humanos , Ratones , Animales , Enfermedad de Alzheimer/patología , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/patología , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Hierro/metabolismo , Receptores de Transferrina/metabolismo , Sobrecarga de Hierro/metabolismo
12.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1027245

RESUMEN

Objective:To analyze the differentially expressed genes in PBMCs of patients with systemic lupus erythematosus (SLE) by bioinformatics methods screening and analyzing the key genes related to ferroptosis, and explore the possible mechanism of ferroptosis involved in the pathogenesis of SLE at the transcription level.Methods:The data sets and samples of healthy people (HC) and SLE patients who met the screening criteria were retrieved from the Gene Expression Omnibus (GEO), a sub-database of the National Center for Biotechnology Information (NCBI). The differentially expressed genes, GO enrichment analysis and KEGG pathway enrichment analysis were analyzed by GEO2R, R language and related software packages. The protein interaction network (PPI) of differential genes was analyzed by STRING, Cytoscape and other tools to explore the key genes and pathways. In addition, real-time quantitative reverse transcription PCR (RT-qPCR) was used to verify the expression of key genes. Mann-Whitney U test was used to compare the expression of key genes in PBMCs between the two groups. Spearman rank correlation analysis was used to explore the relationship between SLE disease activity and the level of key genes. Results:Six data sets were included in this study. A total of 166 genes related to ferroptosis were differentially expressed between SLE and HC groups. The differential genes were specifically expressed in alveolar macrophages, neutrophils, CD49 + cells and CD31 + cells. GO enrichment analysis and KEGG pathway enrichment analysis showed that the differentially expressed genes were mainly involved in multiple signaling pathways closely related to SLE, such as oxidative stress response, infection and TNF signaling pathway. Hub genes screened by different algorithms all suggested RELA as a key gene, and RT-qPCR confirmed that compared with the RELA gene expression level in the HC group [0.75(0.37,1.13)], the expression level in SLE group [2.02 (1.19,4.06)] was increased, the difference was statistically significant ( Z=-3.08, P=0.002), and was positively correlated with the corresponding SLEDAI score of SLE samples ( r=0.52, P=0.019). Conclusion:The ferroptosis of many immune cells, including alveolar macrophages and CD49 + NK cells, is involved in the pathogenesis of SLE. RELA may be involved in the ferroptosis of PBMCs in SLE through the NF-κB pathway.

13.
Chinese Medical Journal ; (24): 950-955, 2018.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-687003

RESUMEN

<p><b>Background</b>Oxidized low-density lipoprotein (ox-LDL)-induced oxidative stress and endothelial apoptosis are essential for atherosclerosis. Our previous study has shown that ox-LDL-induced apoptosis is mediated by the protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2α-subunit (eIF2α)/CCAAT/enhancer-binding protein homologous protein (CHOP) endoplasmic reticulum (ER) stress pathway in endothelial cells. Statins are cholesterol-lowering drugs that exert pleiotropic effects including suppression of oxidative stress. This study aimed to explore the roles of simvastatin on ox-LDL-induced ER stress and apoptosis in endothelial cells.</p><p><b>Methods</b>Human umbilical vein endothelial cells (HUVECs) were treated with simvastatin (0.1, 0.5, or 2.5 μmol/L) or DEVD-CHO (selective inhibitor of caspase-3, 100 μmol/L) for 1 h before the addition of ox-LDL (100 μg/ml) and then incubated for 24 h, and untreated cells were used as a control group. Apoptosis, expression of PERK, phosphorylation of eIF2α, CHOP mRNA level, and caspase-3 activity were measured. Comparisons among multiple groups were performed with one-way analysis of variance (ANOVA) followed by post hoc pairwise comparisons using Tukey's tests. A value of P < 0.05 was considered statistically significant.</p><p><b>Results</b>Exposure of HUVECs to ox-LDL resulted in a significant increase in apoptosis (31.9% vs. 4.9%, P < 0.05). Simvastatin (0.1, 0.5, and 2.5 μmol/L) led to a suppression of ox-LDL-induced apoptosis (28.0%, 24.7%, and 13.8%, F = 15.039, all P < 0.05, compared with control group). Ox-LDL significantly increased the expression of PERK (499.5%, P < 0.05) and phosphorylation of eIF2α (451.6%, P < 0.05), if both of which in the control groups were considered as 100%. Simvastatin treatment (0.1, 0.5, and 2.5 μmol/L) blunted ox-LDL-induced expression of PERK (407.8%, 339.1%, and 187.5%, F = 10.121, all P < 0.05, compared with control group) and phosphorylation of eIF2α (407.8%, 339.1%, 187.5%, F = 11.430, all P < 0.05, compared with control group). In contrast, DEVD-CHO treatment had no significant effect on ox-LDL-induced expression of PERK (486.4%) and phosphorylation of eIF2α (418.8%). Exposure of HUVECs to ox-LDL also markedly induced caspase-3 activity together with increased CHOP mRNA level; these effects were inhibited by simvastatin treatment.</p><p><b>Conclusions</b>This study suggested that simvastatin could inhibit ox-LDL-induced ER stress and apoptosis in vascular endothelial cells.</p>


Asunto(s)
Humanos , Apoptosis , Células Cultivadas , Estrés del Retículo Endoplásmico , Células Endoteliales de la Vena Umbilical Humana , Metabolismo , Lipoproteínas LDL , Farmacología , Oligopéptidos , Farmacología , Simvastatina , Farmacología
14.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-296529

RESUMEN

<p><b>OBJECTIVE</b>PERK/eIF2α/CHOP is a major signaling pathway mediating endoplasmic reticulum (ER) stress related with atherosclerosis. Oxidized LDL (ox-LDL) also induces endothelial apoptosis and plays a vital role in the initiation and progression of atherosclerosis. The present study was conducted to explore the regulatory effect of ox-LDL on PERK/eIF2α/CHOP signaling pathway in vascular endothelial cells.</p><p><b>METHODS</b>The effects of ox-LDL on PERK and p-eIF2α protein expression of primary human umbilical vein endothelial cells (HUVECs) were investigated by Western blot analysis. PERK gene silencing and selective eIF2α phosphatase inhibitor, salubrinal were used to inhibit the process of ox-LDL induced endothelial cell apoptosis, caspase-3 activity, and CHOP mRNA level.</p><p><b>RESULTS</b>Ox-LDL treatment significantly increased the expression of PERK, PERK-mediated inactivation of eIF2α phosphorylation, and the expression of CHOP, as well as the caspase-3 activity and apoptosis. The effects of ox-LDL were markedly decreased by knocking down PERK with stable transduction of lentiviral shRNA or by selective eIF2α phosphatase inhibitor, salubrinal.</p><p><b>CONCLUSION</b>This study provides the first evidence that ox-LDL induces apoptosis in vascular endothelial cells mediated largely via the PERK/eIF2α/CHOP ER-stress pathway. It adds new insights into the molecular mechanisms underlying the pathogenesis and progression of atherosclerosis.</p>


Asunto(s)
Humanos , Apoptosis , Estrés del Retículo Endoplásmico , Factor 2 Eucariótico de Iniciación , Genética , Metabolismo , Células Endoteliales de la Vena Umbilical Humana , Metabolismo , Lipoproteínas LDL , Genética , Metabolismo , Transducción de Señal , Factor de Transcripción CHOP , Genética , Metabolismo , eIF-2 Quinasa , Genética , Metabolismo
15.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-264633

RESUMEN

<p><b>OBJECTIVE</b>To investigate the incidence of falls and recurrent falls, and explore associated factors for single and recurrent falls among urban community-dwelling elderly in Beijing.</p><p><b>METHODS</b>A cross-sectional study was conducted in 472 elderly in the Longtan community of Dongcheng district, Beijing in 2009. Data regarding the incidence of fall and recurrent falls in the previous year, as well as associated factors were collected from the elderly through face-to-face interviews.</p><p><b>RESULTS</b>The incidence of falls and recurrent falls was 17.8% and 6.1%, respectively, and it increased with age (χ2for trend=21.06, 19.20, P=0.001, 0.002). Binary logistic stepwise regression analysis showed that age (OR=2.20), living alone (OR=4.67) and gait disturbance (OR=1.27) were risk factors, while housing with elevators (OR=0.35), appropriate width/height of stair steps (OR=0.78), sufficient lighting for stairway (OR=0.45) and regular exercise (OR=0.12) could lower the risk for single fall; factors such as low monthly family income (OR=1.39), poor vision (OR=1.83), low physical ability (OR=4.47), abnormal static balance (OR=2.48), and fear of falls(OR=2.23) were risk factors, while appropriate width/height of stair steps (OR=0.49) and easiness of access to daily supplies (OR=0.41) were protective factors for recurrent falls.</p><p><b>CONCLUSION</b>The incidence of falls in community-dwelling elderly people in Beijing is common, and falls and their related injuries have been associated with both intrinsic and extrinsic factors.</p>


Asunto(s)
Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Accidentes por Caídas , China , Epidemiología , Ciudades , Incidencia , Recurrencia , Heridas y Lesiones , Epidemiología
16.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-289537

RESUMEN

<p><b>OBJECTIVE</b>To observe the long-term changes in anxiety-like behavior and tyrosine hydroxylase (TH) expression in the substantia nigra (SN) after hypoxic-ischemic brain damage (HIBD) in a neonatal rat model and to further explore the relationship between dopamine (DA) level and long-term anxiety-like behavior using the DA receptor (DAR) antagonist.</p><p><b>METHODS</b>Seven-day-old (P7) neonatal Sprague-Dawley (SD) rats were randomized into normal control, sham-operated, HIBD and HIBD+DAR antagonist groups. HIBD model was prepared by ligating the right common carotid artery and 8% hypoxia exposure. The rats in the sham-operated group were sham-operated and were not subjected to right common carotid artery ligation and hypoxia exposure. The DAR antagonist was injected intraperitoneally before and after inducing HIBD. The same amount of normal saline was given to the other three groups as a control. Anxiety-like behavior was evaluated by elevated plus maze test, and TH expression in the SN was measured by immunohistochemistry on P14, P21, and P28.</p><p><b>RESULTS</b>On P21 and P28, the time spent in the open arms and the percentage of open arms entries in the HIBD group were significantly increased compared with those in the normal control, sham-operated and HIBD+DAR antagonist groups (P<0.05); in addition, the HIBD+DAR antagonist group showed a significantly longer time spent in the open arms than the normal control group (P<0.05). On P14, P21, and P28, TH expression in the HIBD and HIBD+DAR antagonist groups was significantly lower than that in the normal control and sham-operated groups, and TH level in the HIBD group was significantly lower than that in the HIBD+DAR antagonist group (P<0.05).</p><p><b>CONCLUSIONS</b>DAR antagonist allows the restoration of anxiety-like behavior and alleviates the damage to dopaminergic neurons in SD rats after HIBD.</p>


Asunto(s)
Animales , Ratas , Animales Recién Nacidos , Ansiedad , Antagonistas de Dopamina , Usos Terapéuticos , Hipoxia-Isquemia Encefálica , Aprendizaje por Laberinto , Ratas Sprague-Dawley , Receptores Dopaminérgicos , Fisiología , Sustancia Negra , Tirosina 3-Monooxigenasa
17.
Chinese Journal of Pediatrics ; (12): 336-339, 2013.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-359742

RESUMEN

<p><b>OBJECTIVE</b>To quantitatively assess the association between transfusions and the risk of necrotizing enterocolitis (NEC) in neonates.</p><p><b>METHOD</b>Both Chinese and English literature published from Jan. 1985 to Nov. 2011 about the case-control study of the association between transfusions and neonatal NEC were retrieved by searching the electronic resource databases. A meta-analysis was then performed on the comparison and synthesis of findings from included studies. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using RevMan 5.0 software. Sensitivity analysis was conducted and possible publication bias was tested as well.</p><p><b>RESULT</b>A total of 7 case-control studies (480 blood transfusion cases, 2845 control cases) were included. The meta-analysis with a random-effects model found a pooled OR of 3.35 (95% CI: 1.54-7.27). Sensitivity analysis showed that OR for post-transfusion NEC within 48 h was 4.21 (95% CI: 2.17-8.16). The OR was 4.29 (95% CI: 1.39-13.24) after factors such as gestational age and birth weight were de-confounded. The fail-safe number was 263.</p><p><b>CONCLUSION</b>Blood transfusion can increase the risk of NEC in neonates. The clinical application of this conclusion should be cautious due to limited reports. High-quality randomized control trials are still needed for the further proof of the association between blood transfusion and neonatal NEC.</p>


Asunto(s)
Femenino , Humanos , Recién Nacido , Masculino , Sesgo , Estudios de Casos y Controles , Enterocolitis Necrotizante , Epidemiología , Enfermedades del Recién Nacido , Epidemiología , Terapéutica , Recien Nacido Prematuro , Descubrimiento del Conocimiento , Oportunidad Relativa , Factores de Riesgo , Reacción a la Transfusión
18.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-320331

RESUMEN

<p><b>OBJECTIVE</b>The mechanism through which platelet activating factor (PAF) induces cardiac electrical activity and arrhythmia is not well understood and previous studies have suggested a potential involvement of ion channels in its action. The present study was aimed to clarify the role of PAF in fatal arrhythmias following acute myocardia infarction (AMI) and the underlying mechanism.</p><p><b>METHODS</b>(1) Blood PAF levels were measured among 72 AMI patients at the time of diagnosis with AMI and 48 h later, and their electrocardiogram (ECG) was recorded continuously. (2) Ischemia simulation and surface electrocardiogram were conducted in 20 pigs and their PAF levels were measured. (3) PAF perfusion and standard microelectrode recording were performed on guinea pig papillary muscles.</p><p><b>RESULTS</b>In both humans and pigs, elevated PAF levels were detected in AMI and simulated ischemia, respectively, and even higher PAF levels were found when fatal arrhythmias occurred. In guinea pig myocardium, PAF induced a shortening of action potential duration at 90% level of repolarization (APD90)under non-ischemic conditions and a more pronounced shortening under early simulated ischemic conditions.</p><p><b>CONCLUSION</b>AMI and ischemia are associated with increased PAF levels in humans and pigs, which are further raised when fatal arrhythmia follows. The effects of PAF on the myocardium may be mediated by multiple ion channels.</p>


Asunto(s)
Animales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arritmias Cardíacas , Sangre , Electrocardiografía , Corazón , Isquemia Miocárdica , Sangre , Factor de Activación Plaquetaria , Metabolismo , Porcinos
19.
Chinese Journal of Epidemiology ; (12): 967-969, 2013.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-320961

RESUMEN

<p><b>OBJECTIVE</b>To investigate the incidence and risk factors for recurrent falls in community-dwelling elderly in Beijing.</p><p><b>METHODS</b>A cross-sectional study was conducted in 472 elderly in the Longtan community of Dongcheng district,Beijing in 2009. Data on recurrent falls within the past 12 months were collected through face-to-face interview, with both single factor analysis and logistic regression analysis used to explore the related factors on recurrent falls in the elderly.</p><p><b>RESULTS</b>The incidence of recurrent falls among 472 older adults was 6.1% (29) within the past 12 months. Results from logistic regression analysis showed that factors as higher family monthly income(OR = 1.39, 95% CI:0.67-2.16), afraid of being fallen(OR = 2.23, 95% CI:1.47-3.85)and abnormal static balance(OR = 2.48, 95% CI:1.84-4.05)were risk factors, while bench height in the surrounding environment(OR = 0.49, 95% CI:0.21-1.12)and easiness of access to daily supplies (OR = 0.41, 95%CI:0.14-1.16)were protective factors for recurrent falls.</p><p><b>CONCLUSION</b>The incidence of recurrent falls among the elderly from the communities in Beijing was high. Since falls could be caused by various factors, intervention should be targeting on risk factors in a multi-dimensional way.</p>


Asunto(s)
Anciano , Femenino , Humanos , Masculino , Accidentes por Caídas , China , Epidemiología , Incidencia , Modelos Logísticos , Factores de Riesgo
20.
Chinese Journal of Cardiology ; (12): 106-109, 2011.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-244044

RESUMEN

<p><b>OBJECTIVE</b>To analyze the clinical characteristics and prognosis of Chinese patients with apical hypertrophic cardiomyopathy (AHCM).</p><p><b>METHODS</b>A total of 188 patients with AHCM diagnosed at Fuwai Hospital were included in this retrospective study. Clinical characteristics, mortality and cardiovascular morbidity were analyzed. A multiple logistic regression was performed to adjust for potential confounding factors.</p><p><b>RESULTS</b>Males predominated with a number of 139 (73.9%) in this cohort. Patient's age ranged from 15 to 81 (51.9 ± 12.6) years. There were 120 patients (63.8%) with "pure" type and 68 patients (36.2%) with "mixed" type of AHCM, 171 patients were followed up for (5.0 ± 3.0) years, cardiovascular mortality was 1.2%, 28 patients (16.4%) experienced one or more cardiovascular events.</p><p><b>CONCLUSION</b>The prevalence of AHCM is high in Chinese HCM patients, pure type AHCM is more common, and AHCM patients have a benign clinical course.</p>


Asunto(s)
Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Cardiomiopatía Hipertrófica , Diagnóstico , Epidemiología , Pronóstico , Estudios Retrospectivos
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